Engineering a human-based translational activator for targeted protein expression restoration - PubMed
5 days ago
- #translational activation
- #Dravet syndrome
- #haploinsufficiency
- Therapeutic modalities to increase protein production are needed for diseases caused by haploinsufficiency.
- A translational activator was engineered using the CRISPR-Cas-inspired RNA-targeting system (CIRTS) platform.
- The engineered human protein, CIRTS-4GT3, can increase mRNA translation by up to 100% for specific transcripts.
- AAV-delivery of CIRTS-4GT3 targeting SCN1a mRNA improved survivability and seizure threshold in a Dravet syndrome mouse model.
- This approach validates a strategy to address SCN1a haploinsufficiency and highlights the potential of translational activation for neurological disorders.